The pathogenesis of mitochondrial disease is expected to develop targeted therapeutic drugs

January 29, 2018 Source: Science and Technology Daily

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A recent study by the research team of Professor Wei Fanyan of Kumamoto University and Professor Suzuki of the University of Tokyo found that a functional Amino Acid called taurine plays an important role in the production and preservation of proteins in and out of the mitochondria. Experiments show that through specific Chemicals maintain protein quality and can improve the symptoms of mitochondrial diseases.

Mitochondria are "energy manufacturing plants" in eukaryotic cells that contain thousands of proteins that maintain the functions of mitochondria. If the genes encoding these proteins are mutated, mitochondrial diseases of central nervous system or various organ abnormalities may occur. There is no effective treatment for mitochondrial diseases, and the frequency of onset is about 9 to 15 in 100,000 people. There are various types of mitochondrial diseases. Most of the mitochondrial myopathy is MELAS and MERRF. Symptoms are generalized muscle weakness and poor cardiac function. Most patients die several years later.

So far, the pathogenesis of MELAS and MERRF is unknown, and it has been reported that taurine is involved. Previous studies have found that taurine has a low binding to tRNA in patients with MELAS and MERRF, but it is not known why the decline in taurine function can cause serious illness.

The research team used advanced methods such as mass analysis and genetic engineering to find that taurine is indispensable for protein synthesis in mitochondria. Investigations using cells with low taurine function and model mice showed that protein production in mitochondria was almost stagnant and mitochondrial function and structure were disrupted. As a result, various proteins produced by the cytoplasm and delivered to the mitochondria lose their orientation, causing structural destruction of the protein, and forming a highly toxic agglomerated volume in the cytoplasm. When the model rats were allowed to take a compound that inhibited the coagulation volume and reduced the function of taurine, the toxicity of the aggregate decreased, and the symptoms of mitochondrial disease were alleviated.

The research results are published this month in the online edition of the Cell Report. (Reporter Chen Chao)

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